Tagraxofusp Shows On-Target/Bone Marrow-Sparing Effects in First-Line BPDCN

Frontline treatment with tagraxofusp-erzs (Elzonris) exhibited on-target, bone marrow-sparing effects among patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to findings from a post hoc analysis of a phase 2 trial (NCT02113982) published in Cancer.¹

Specifically, among patients with baseline bone marrow involvement, the neutrophil counts were below the normal range at baseline, defined as 2.6 to 8.0 x 10⁹/L at baseline, gradually increasing throughout the course of treatment and returning to normal within the first 4 cycles of tagraxofusp. Among those without baseline bone marrow involvement, neutrophil counts remained within a normal range for the duration of treatment. Additionally, in both groups, G-CSF was concentrated in the first few tagraxofusp cycles, with a greater amount given to patients with baseline bone marrow involvement.

Furthermore, among 32 patients not previously treated for their BPDCN with baseline bone marrow involvement, 17 achieved a complete response (CR) or clinical complete response (CCR) compared with 15 who did not. In each group, a median of 6 cycles (range, 1-76) and 2 cycles (range, 1-4) were administered.

“The rapid and durable responses observed with tagraxofusp in the pivotal trial, coupled with its unique safety profile, lack of cumulative myelosuppression, and restoration of normal hematopoiesis during treatment demonstrated in this analysis, support tagraxofusp monotherapy as a standard of care for patients with treatment-naive BPDCN,” Marina Konopleva, MD, PhD, professor in the Department of Medical Oncology and Cell Biology and Miriam Mandel Faculty Scholer in Cancer Research at the Albert Einstein College of Medicine, wrote in the publication with study coinvestigators.¹“[T]agraxofusp is a safe and promising partner for combination therapy in patients with myelosuppressive CD123-positive hematologic malignancies, such as acute myeloid leukemia [AML], myelodysplastic syndrome, and chronic myelomonocytic leukemia, for which the disease itself and most other available combination therapy partners are myelosuppressive.”

Additional data revealed that among patients with baseline bone marrow involvement, the platelet counts at baseline were below the normal range, defined as 150 to 350 x 10⁹/L, and increased to normal by the start of cycle 2 after attaining a nadir at day 8 and 15 of cycle 1. Furthermore, platelet counts among those without bone marrow involvement at baseline fell below the normal range but stabilized by cycle 2. Those requiring platelet transfusions during treatment with tagraxofusp declined after cycle 1 in both groups, with a greater decline observed among those with baseline bone marrow involvement vs those without.

Finally, for the bone-marrow–involved group, hemoglobin levels rose during day 1 and increased slightly with subsequent cycles of tagraxofusp, and hemoglobin levels increased post-tagraxofusp over time. In those without bone marrow involvement, a more pronounced rise in hemoglobin levels was observed throughout treatment. Fewer patients required red blood cell transfusions in both groups between cycles 1 and 4; from 35% to 12% in the bone marrow-involved group vs 9% to 5% in those without bone marrow involvement.

Patients in the 4-stage phase 2 study received tagraxofusp in 21-day cycles. In stage 1, the maximum tolerated dose (MTD) of tagraxofusp was determined, and stage 2 was a cohort expansion to determine its efficacy and safety at the MTD.² Stages 3 and 4 were conducted to determine the efficacy and safety of the agent in first-line BPDCN alone and first-line as well as relapsed/refractory BPCDN, respectively.

For the post hoc analysis, the treatment-naïve group was stratified by bone marrow involvement. The analysis assessed neutrophil levels, platelet counts, hemoglobin levels, and peripheral leukemic blasts throughout the first 4 cycles of treatment. In the groups with (n =32) and without bone marrow involvement (n = 34), respectively, the median age was 69 years (range, 22-82) vs 66 years (range, 22-84), 78% vs 82% of patients were female, 84% vs 91% were White, and 88% vs 94% were non-Hispanic. A total of 66% in the bone-marrow–involved group had an ECOG performance status of 1 vs 71% of those without bone marrow involvement having a status of 0, 97% vs 41% had disease involvement at 2 or more disease sites.

References

1. Konopleva M, Pemmaraju N, Sweet KL, et al. Hematopoietic effects of tagraxofusp in treatment-naive patients with blastic plasmacytoid dendritic cell neoplasm. Cancer. 2026;132(1):e70243. doi:10.1002/cncr.70243
2. Tagraxofusp in patients with blastic plasmacytoid dendritic cell neoplasm or acute myeloid leukemia. ClinicalTrials.gov. Updated August 1, 2024. Accessed January 13, 2026. https://tinyurl.com/2fyd4bu2